We propose to investigate the immunochemistry, structure, and function of human melanoma-asociated antigen p97, one of the best characterized and most tumor-specific of the human tumor-associated antigens so far indentified by monoclonal antibodies. Work that we have done over the past 3 years has provided the background for these studies. Our goal is to use p97 as a model so as to obtain insight into the nature of human tumor-associated oncofetal antigens, and to open the way to more effective diagnosis and therapy of human cancer. We have 3 specific aims: 1. Immunochemistry of p97: We propose (a) to generate and characterize monoclonal antibodies to additional epitopes of native and denatured p97, (b) to synthesize peptides based on the amino acid sequence of p97 for use as immunogens, and (c) to obtain anti-idiotypic antibidies to mimic conformational epitopes of p97 for use as immunogens. 2. Structure of p97: Our structural studies of p97 will comprise (a) amino acid sequencing, (b) investigation of post-translation modifications, particularly carbohydrate and phosphate, and (c) examination of its structure at the cell surface. 3. Function of p97: We shall investigate (a) the putative role of p97 in iron uptake, particularly to determine whether p97 offers an alternative to the transferrin receptor as means of iron uptake by melanoma cells, and (b) the association of p97 with neoplasia, particularly whether the presence of p97 in large amounts in melanomas is a consequence (or cause) of neoplastic transformation or rapid growth.